The radionuclides Ga67, In111, Bi206 and the rare earths have been found to have affinities for soft tissue tumor in both animals and man. The aim of this project is to determine the mechanism(s) and biochemical agent(s) involved in the deposition of these materials in both normal and malignant tissues. We plan to test various means for separating in a high state of purity the small subcellular granules (as opposed to normal lysosomes) that have been shown to be responsible for most of the particulate binding of Ga67, In111, and rare earth radionuclides in tumor cells (as opposed to normal cells) so that the exact nature of these particles may be determined. Bismuth-206 has a different distribution and a more precise separation of those organelles that bind it will also be attempted. Chromatographic and electrophoretic techniques along with various automated bioanalytical techniques will be used to determine the nature of the 5-4 x 10 to the 4th power MW macromolecular component(s) that account for a high proportion of the binding of Ga67, In111, and rare earth radionuclides in extracts of tumor and thymus tissue (as contrasted with that seen in other normal tissues). Tissue cultures are now being used to determine in different cell lines what factors in the culture media lead to Ga67 uptake and whether the uptake observed is reversible or not.